The filtration of sub-micron aerosol by a nanofiber medium with fiber diameter 100 - 400 nm is of great interest. For different polymeric materials, we found that both Poly-ethylene Oxide (PEO) nanofiber with fiber diameter 200 nm (fabricated in-house), or other polymeric nanofiber filters with fiber diameter 300 nm (acquired elsewhere), can both remove effectively 50 - 500 nm aerosol generated from a controlled aerosol source. The Payet model, which was originally developed for microfiber filter with Knudsen number of fiber (Knf) smaller than 0.1 under the assumption of continuum physics, has been demonstrated to predict the filtration of 50 - 500 nm aerosol using nanofiber filter with much larger Knf from 0.4 - 0.6 (transition regime for airflow) for filters with a wide range of solidosity (0.004 - 0.036) and fiber diameter (200 - 300 nm). For filtering these sub-micron aerosols, diffusion and interception by nanofibers has been found to be the dominant mechanisms due to large surface area-to-volume ratio of the nanofibers. In particular, we found good agreement on the diffusion capture mechanism on sub-micron aerosol between Payet’s model and our experimental results for low Peclet number (Pe), i.e. a measure of convective transport to molecular diffusion, from 5 to 50 by varying the filter solidosity and face velocity. This range of Pe is much below what had been reported heretofore in the literature of over 1000. Nanofiber can be a good filter medium or a coating on an existing medium. In either case, the filtration performance is higher compared to that of microfiber filter. The disadvantage is that pressure drop is high especially for increasing amount of nanofiber in the filter which can achieve high filtration efficiency. Another part of our research is to develop novel methods to mitigate pressure drop for both clean and loaded nanofiber filters. For clean filter, we have developed a novel multi-layering method wherein nanofibers are separately spaced out in web / mesh with support material as compared with having the same amount of nanofibers coated or deposited on a single-layer. This reduces pressure drop while achieving a very high filtration efficiency. This has been demonstrated by a reduction of pressure drop by 58 % using 12 layers of nanofiber with each layer having basis weight 0.06 gm⁻² when compared to a single layer of nanofiber with the same total basis weight of 0.7 gm⁻².For loaded filter, a dual-layer filter with microfibers upstream and nanofibers downstream was developed. This composite arrangement was found to reduce the skin layer effect (i.e. the large pressure drop across a short distance especially at the upstream face of nanofiber layer) by more evenly distributing the captured aerosols in both the microfiber and nanofiber layers. A second method to reduce pressure drop in a loaded nanofiber filter is to back-pulse the nanofiber filter by pulsating air jet from the downstream end to discharge the deposited aerosol. This allows the filter to temporarily accumulate the solids as measured by pressure drop in excess of a threshold level before back-pulsing. Our test under 60 hours of repeated loading and regeneration shows the increase in residual pressure drop by 64 Pa under an imposed threshold pressure drop of 300 Pa. This threshold pressure drop can be increased to over 1200 Pa for enhanced storage capacity in between cleaning. We have also developed a model to explain the loading characteristics of the nanofiber filter as measured by a pressure drop. For light loading, aerosol build-up can be explained by a model wherein aerosol deposit surrounds each fiber, whereas at high solids loading, aerosol build-up in form of dendrites can be modeled by additional "deposit fibers". Both models respectively at light to high solids loading compare well with the pressure drop measured experimentally. In addition, a model was developed to estimate the deposition profile (i.e. distribution of deposit mass, along filter thickness) including inhomogeneous filter with separate microfiber and nanofiber layers and challenged by polydisperse aerosol stream. This model is an improvement over past model which deals only with homogeneous filter containing single-size fibers challenged by monodisperse aerosol. This model helps to explain the much faster pressure drop increase rate of nanofiber filter and also the effectiveness of dual-layer media on mitigating filter clogging.